Association of leptin receptor expression in placenta and peripheral blood mononuclear cell with maternal weight in birth outcomes.

INTRODUCTION: The pregnancy period represents the most intense period of growth and development. Pre-pregnancy weight influences weight gain during pregnancy. Leptin is a hormone mainly derived from white adipose tissue, during pregnancy leptin is also produced by the placenta. It has been suggested that the effects of placental leptin on the mother may contribute to endocrine-mediated alterations in energy balance; a dysregulation in leptin levels or its receptors may lead to poor birth outcomes. Therefore, the main goal of the present study was to analyze the differences in birth outcomes by maternal weight with the expression level of leptin receptor in maternal peripheral blood mononuclear cell (PBMC) and placental tissue. METHODS: Women with full-term gestation and its offspring were enrolled. Total RNA from maternal PBMC and placenta was obtained to perform the analysis of expression of the leptin receptor (LEPR) gene trough real-time PCR technique. Data were analyzed using one-way ANOVA or Mann-Whitney u test when applicable. Pearson correlation coefficient was used to determine the relationship between continuous variables (Stata v.13); p ≤ 0.05 was considered statistically significant. RESULTS: No statistically significant differences were found between LEPR expression level and the BMI studied groups in maternal PBMC and placental tissue. Interaction between gestational weight gain (GWG) and LEPR in maternal PBMC explain in a 32% the variability of the newborn weight. CONCLUSIONS: LEPR expression level in maternal PBMC correlates with newborn measurements independent from sex. GWG can affect fetal development by increasing fetal birth weight.

Src family kinases are required for prolactin induction of cell proliferation.

Prolactin (PRL) is a pleiotropic cytokine promoting cellular proliferation and differentiation. Because PRL activates the Src family of tyrosine kinases (SFK), we have studied the role of these kinases in PRL cell proliferation signaling. PRL induced [(3)H]thymidine incorporation upon transient transfection of BaF-3 cells with the PRL receptor. This effect was inhibited by cotransfection with the dominant negative mutant of c-Src (K>A295/Y>F527, SrcDM). The role of SFK in PRL-induced proliferation was confirmed in the BaF-3 PRL receptor-stable transfectant, W53 cells, where PRL induced Fyn and Lyn activation. The SFK-selective inhibitors PP1/PP2 and herbimycin A blocked PRL-dependent cell proliferation by arresting the W53 cells in G1, with no evident apoptosis. In parallel, PP1/PP2 inhibited PRL induction of cell growth-related genes c-fos, c-jun, c-myc, and odc. These inhibitors have no effect on PRL-mediated activation of Ras/Mapk and Jak/Start pathways. In contrast, they inhibited the PRL-dependent stimulation of the SFKs substrate Sam68, the phosphorylation of the tyrosine phosphatase Shp2, and the PI3K-dependent Akt and p70S6k serine kinases. Consistently, transient expression of SrcDM in W53 cells also blocked PRL activation of Akt. These results demonstrate that activation of SFKs is required for cell proliferation induced by PRL.

Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer.

Oral mucosal colonization and infection with Candida are common in patients receiving radiation therapy for head and neck cancer. Infection is marked by oral pain and/or burning and can lead to significant patient morbidity. The purpose of this study was to identify Candida strain diversity in this population by using a chromogenic medium, subculturing, molecular typing, and antifungal susceptibility testing of clinical isolates. These results were then correlated with clinical outcome in patients treated with fluconazole for infection. Specimens from 30 patients receiving radiation therapy for head and neck cancer were cultured weekly for Candida. Patients exhibiting clinical infection were treated with oral fluconazole. All isolates were plated on CHROMagar Candida and RPMI medium, subcultured, and submitted for antifungal susceptibility testing and molecular typing. Infections occurred in 27% of the patients and were predominantly due to Candida albicans (78%). Candida carriage occurred in 73% of patients and at 51% of patient visits. Yeasts other than C. albicans predominated in carriage, as they were isolated from 59% of patients and at 52% of patient visits. All infections responded clinically, and all isolates were susceptible to fluconazole. Molecular typing showed that most patients had similar strains throughout their radiation treatment. One patient, however, did show the acquisition of a new strain. With this high rate of infection (27%), prophylaxis to prevent infection should be evaluated for these patients.